AIM:To investigate the effect of Chai-Qin-Cheng-Qi Decoction(CQCQD)on cefotaxime(CTX)concentration in pancreas of rats with acute necrotizing pancreatitis (ANP). METHODS:Sixty healthy male Sprague-Dawley rats were div...AIM:To investigate the effect of Chai-Qin-Cheng-Qi Decoction(CQCQD)on cefotaxime(CTX)concentration in pancreas of rats with acute necrotizing pancreatitis (ANP). METHODS:Sixty healthy male Sprague-Dawley rats were divided randomly into an ANP group(ANP model +CTX,n=20),treatment group(ANP model+CTX +CQCQD,n=20)and control group(normal rats+ CTX,n=20).ANP models were induced by retrograde intraductal injection of 3.5%sodium taurocholate (1 mL/kg),and the control group was injected intraductally with normal saline.All rats were injected introperitoneally with 0.42 g/kg CTX(at 12-h intervals for a continuous 72 h)at 6 h after intraductal injection. Meanwhile,the treatment group received CQCQD (20 mL/kg)intragastrically at 8-h intervals,and the ANP and control group were treated intragastrically with normal saline.At 15 min after the last CTX injection,blood and pancreas samples were collected for the determination of CTX concentration using validated high-performance liquid chromatography. Pathological changes and wet-to-dry-weight(W/D) ratio of pancreatic tissue were examined. RESULTS:Serum CTX concentrations in three groups were not significantly different.Pancreatic CTXconcentration and penetration ratio were lower in ANP group vs control group(4.4±0.6μg/mL vs 18.6± 1.7μg/mL,P=0.000;5%vs 19%,P=0.000),but significantly higher in treatment group vs ANP group (6.4±1.7μg/mL vs 4.4±0.6μg/mL,P=0.020;7% vs 5%,P=0.048).The histological scores and W/D ratio were significantly decreased in treatment group vs ANP and control group. CONCLUSION:CQCQD might have a promotive effect on CTX concentration in pancreatic tissues of rats with ANP.展开更多
Erythromycin is a commonly used broad-spectrum antibiotic,but resistance to this antibiotic makes its use less effective.Considerable efforts,beside finding alternatives,are needed to enhance its antimicrobial effect ...Erythromycin is a commonly used broad-spectrum antibiotic,but resistance to this antibiotic makes its use less effective.Considerable efforts,beside finding alternatives,are needed to enhance its antimicrobial effect and stability against bacteria.Tetrahedral framework nucleic acids(tFNAs),a novel delivery vehicle with a three-dimensional nanostructure,have been studied as a carrying platform of antineoplastic drugs.In this study,the use of tFNAs in delivering erythromycin into Escherichia coli(E.coli)was investigated for the first time.The tFNAs vehicle increased the bacterial uptake of erythromycin and promoted membrane destabilization.Moreover,it increased the permeability of the bacterial cell wall,and reduced drug resistance by improving the movement of the drug across the membrane.The tFNAs-based delivery system enhanced the effects of erythromycin against E.coli.It may therefore provide an effective delivery vehicle for erythromycin in targeting antibiotic-resistant bacteria with thick cell wall.展开更多
The limited penetration of nanoparticles and their poor accessibility to cancer cell fractions in tumor remain essential challenges for effective anticancer therapy.Herein,we designed a targeting peptide-decorated bio...The limited penetration of nanoparticles and their poor accessibility to cancer cell fractions in tumor remain essential challenges for effective anticancer therapy.Herein,we designed a targeting peptide-decorated biomimetic lipoprotein(termed as BL-RD)to enable their deep penetration and efficient accessibility to cancer cell fractions in a tumor,thereby improving the combinational chemophotodynamic therapy of triple negative breast cancer.BL-RD was composed of phospholipids,apolipoprotein A1 mimetic peptide(PK22),targeting peptide-conjugated cytotoxic mertansine(RM)and photodynamic agents of DiIC18(5)(DiD).The counterpart biomimetic lipoprotein system without RM(termed as BL-D)was fabricated as control.Both BL-D and BL-RD were nanometer-sized particles with a mean diameter of less than 30 nm and could be efficiently internalized by cancer cells.After intravenous injection,they can be specifically accumulated at tumor sites.When comparing to the counterpart BLD,BL-RD displayed superior capability to permeate across the tumor mass,extravasate from tumor vasculature to distant regions and efficiently access the cancer cell fractions in a solid tumor,thus producing noticeable depression of the tumor growth.Taken together,BL-RD can be a promising delivery nanoplatform with prominent tumor-penetrating and cancer cells-accessing capability for effective tumor therapy.展开更多
Photodynamic therapy(PDT)has been applied in clinical treatment of tumors for a long time.However,insufficient supply of pivotal factors including photosensitizer(PS),light,and oxygen in tumor tissue dramatically redu...Photodynamic therapy(PDT)has been applied in clinical treatment of tumors for a long time.However,insufficient supply of pivotal factors including photosensitizer(PS),light,and oxygen in tumor tissue dramatically reduces the therapeutic efficacy of PDT.Nanoparticles have received an influx of attention as drug carriers,and recent studies have demonstrated their promising potential to overcome the obstacles of PDT in tumor tissue.Physicochemical optimization for passive targeting,ligand modification for active targeting,and stimuli-responsive release achieved efficient delivery of PS to tumor tissue.Various trials using upconversion NPs,two-photon lasers,X-rays,and bioluminescence have provided clues for efficient methods of light delivery to deep tissue.Attempts have been made to overcome unfavorable tumor microenvironments via artificial oxygen generation,Fenton reaction,and combination with other chemical drugs.In this review,we introduce these creative approaches to addressing the hurdles facing PDT in tumors.In particular,the studies that have been validated in animal experiments are preferred in this review over proof-of-concept studies that were only performed in cells.展开更多
Current antibody–drug conjugates(ADCs)suffer from low tissue penetration and significant side effects,largely due to the permanent linkage and/or premature release of cytotoxic payloads.Herein,we developed a prodrug...Current antibody–drug conjugates(ADCs)suffer from low tissue penetration and significant side effects,largely due to the permanent linkage and/or premature release of cytotoxic payloads.Herein,we developed a prodrug–antibody conjugate(ProADC)strategy by conjugating a bioorthogonal-activatable prodrug with an antibody that allowed on-target release and on-demand activation of cytotoxic drugs at a tumor site.The bioorthogonal-caged prodrug exhibited an enhanced permeability into and on-demand activation within cancer cells,while the pH-sensitive ADC linker allowed on-target release of the anticancer agent.Together,the ProADCs showed enhanced tumor penetration and alleviated side effects for use as an on-target and on-demand chemotherapy agents.展开更多
Peptide-drug conjugates have achieved considerable development and application as a novel strategy for targeted delivery of anticancer drugs. Bioactive peptides induced calcium deposition can irreversibly assist inhib...Peptide-drug conjugates have achieved considerable development and application as a novel strategy for targeted delivery of anticancer drugs. Bioactive peptides induced calcium deposition can irreversibly assist inhibition of tumors. However, active regulation of calcium level through signal transduction of bioactive substances has not been reported yet. In this study, novel neuropeptide-doxorubicin conjugates(NP-DOX) with lysosome-specific acid response were described for neuropeptide Y_1 receptor(Y_1R)-overexpressed triple-negative breast cancer. The delivery mechanism of NP-DOX was clarified that diverse pathways were involved, including intracellular and intercellular transport. Importantly, up-regulation of Y_1 R-mediated intracellular calcium level via second messenger inositol triphosphate was presented in NP-DOX treated MDA-MB-231 cells. In vivo antitumor efficacy demonstrated that NP-DOX showed less organ toxicity and enhanced tumor inhibition benefited from its controlled release and Y_1R-mediated calcium deposition, compared with free DOX. This bioconjugate is a proof-of-concept confirming that neuropeptide-mediated control of signaling responses in neuropeptide-drug conjugates enables great potential for further applications in tumor chemotherapy.展开更多
Numerous systems have been designed during the past three decades to improve bioavailability of ophthalmic drug delivery,including:ocular prodrugs and nanotechnology-based drug delivery system.The former can improve t...Numerous systems have been designed during the past three decades to improve bioavailability of ophthalmic drug delivery,including:ocular prodrugs and nanotechnology-based drug delivery system.The former can improve the efficacy of ocular drug via enhancing corneal penetration of ocular drugs,prolonging their duration of action and/or reducing the systemic side-effects,unfortunately,some characteristics of the pro-drugs,such as poorly aqueous stability,poorly aqueous solubility and severe eye irritation probably,limit their clinical practice and cannot be ignored.As we all know,nanotech-nology for ocular drug delivery can carry poorly soluble drugs,protect the encapsulated molecules from hydrolysis,control the rate of drug delivery and prolong the precorneal retention of drugs.All of these merits may solve the problems in the utilization of ocular prodrugs and increase the bioavailability of ocular drug delivery.By reviewing recent ad-vances of prodrugs and nanostructures in ocular drug delivery,this paper focus specifically on the promising prospects of nanocarriers overcoming the drawbacks of prodrugs for ophthalmic drug delivery by precorneal routes.展开更多
Nano materials is a new type of drug carriers with very promising application. In recent years, great progress was achieved in making drugs own the characteristics of targeted and con-trolled release via nanotechnolog...Nano materials is a new type of drug carriers with very promising application. In recent years, great progress was achieved in making drugs own the characteristics of targeted and con-trolled release via nanotechnologies. This paper addressed the capability of nano drugs on tar-geting to cells, penetrating through epicyte, controlled release and the security issues re-sulting from its using. We gave the prospect of nano drugs in biology and medicine applying.展开更多
基金Supported by National Key Technology R&D Program of China,No.2006BAI04A15Major Diseases Fund of Sichuan Province Administration of Traditional Chinese Medicine,No.2007B03
文摘AIM:To investigate the effect of Chai-Qin-Cheng-Qi Decoction(CQCQD)on cefotaxime(CTX)concentration in pancreas of rats with acute necrotizing pancreatitis (ANP). METHODS:Sixty healthy male Sprague-Dawley rats were divided randomly into an ANP group(ANP model +CTX,n=20),treatment group(ANP model+CTX +CQCQD,n=20)and control group(normal rats+ CTX,n=20).ANP models were induced by retrograde intraductal injection of 3.5%sodium taurocholate (1 mL/kg),and the control group was injected intraductally with normal saline.All rats were injected introperitoneally with 0.42 g/kg CTX(at 12-h intervals for a continuous 72 h)at 6 h after intraductal injection. Meanwhile,the treatment group received CQCQD (20 mL/kg)intragastrically at 8-h intervals,and the ANP and control group were treated intragastrically with normal saline.At 15 min after the last CTX injection,blood and pancreas samples were collected for the determination of CTX concentration using validated high-performance liquid chromatography. Pathological changes and wet-to-dry-weight(W/D) ratio of pancreatic tissue were examined. RESULTS:Serum CTX concentrations in three groups were not significantly different.Pancreatic CTXconcentration and penetration ratio were lower in ANP group vs control group(4.4±0.6μg/mL vs 18.6± 1.7μg/mL,P=0.000;5%vs 19%,P=0.000),but significantly higher in treatment group vs ANP group (6.4±1.7μg/mL vs 4.4±0.6μg/mL,P=0.020;7% vs 5%,P=0.048).The histological scores and W/D ratio were significantly decreased in treatment group vs ANP and control group. CONCLUSION:CQCQD might have a promotive effect on CTX concentration in pancreatic tissues of rats with ANP.
基金This study was funded by the National Key R&D Program of China[2019YFA0110600]and National Natural Science Foundation of China [81970916, 81671031].
文摘Erythromycin is a commonly used broad-spectrum antibiotic,but resistance to this antibiotic makes its use less effective.Considerable efforts,beside finding alternatives,are needed to enhance its antimicrobial effect and stability against bacteria.Tetrahedral framework nucleic acids(tFNAs),a novel delivery vehicle with a three-dimensional nanostructure,have been studied as a carrying platform of antineoplastic drugs.In this study,the use of tFNAs in delivering erythromycin into Escherichia coli(E.coli)was investigated for the first time.The tFNAs vehicle increased the bacterial uptake of erythromycin and promoted membrane destabilization.Moreover,it increased the permeability of the bacterial cell wall,and reduced drug resistance by improving the movement of the drug across the membrane.The tFNAs-based delivery system enhanced the effects of erythromycin against E.coli.It may therefore provide an effective delivery vehicle for erythromycin in targeting antibiotic-resistant bacteria with thick cell wall.
基金financially supported by the National Basic Research Program of China(2015CB932103)the National Natural Science Foundation of China(31771092,81521005,81690265)the Youth Innovation Promotion Association of Chinese Academy of Sciences and Fudan-SIMM Joint Research Fund(FU-SIMM20182005,China).
文摘The limited penetration of nanoparticles and their poor accessibility to cancer cell fractions in tumor remain essential challenges for effective anticancer therapy.Herein,we designed a targeting peptide-decorated biomimetic lipoprotein(termed as BL-RD)to enable their deep penetration and efficient accessibility to cancer cell fractions in a tumor,thereby improving the combinational chemophotodynamic therapy of triple negative breast cancer.BL-RD was composed of phospholipids,apolipoprotein A1 mimetic peptide(PK22),targeting peptide-conjugated cytotoxic mertansine(RM)and photodynamic agents of DiIC18(5)(DiD).The counterpart biomimetic lipoprotein system without RM(termed as BL-D)was fabricated as control.Both BL-D and BL-RD were nanometer-sized particles with a mean diameter of less than 30 nm and could be efficiently internalized by cancer cells.After intravenous injection,they can be specifically accumulated at tumor sites.When comparing to the counterpart BLD,BL-RD displayed superior capability to permeate across the tumor mass,extravasate from tumor vasculature to distant regions and efficiently access the cancer cell fractions in a solid tumor,thus producing noticeable depression of the tumor growth.Taken together,BL-RD can be a promising delivery nanoplatform with prominent tumor-penetrating and cancer cells-accessing capability for effective tumor therapy.
基金supported by Basic Research Program(2016R1C1B3013951,2021R1F1A1061286,and 2021R1A4A3031875)through the National Research Foundation of Korea(NRF)funded by the Korean government(Ministry of Science,ICT,and Future Planning).
文摘Photodynamic therapy(PDT)has been applied in clinical treatment of tumors for a long time.However,insufficient supply of pivotal factors including photosensitizer(PS),light,and oxygen in tumor tissue dramatically reduces the therapeutic efficacy of PDT.Nanoparticles have received an influx of attention as drug carriers,and recent studies have demonstrated their promising potential to overcome the obstacles of PDT in tumor tissue.Physicochemical optimization for passive targeting,ligand modification for active targeting,and stimuli-responsive release achieved efficient delivery of PS to tumor tissue.Various trials using upconversion NPs,two-photon lasers,X-rays,and bioluminescence have provided clues for efficient methods of light delivery to deep tissue.Attempts have been made to overcome unfavorable tumor microenvironments via artificial oxygen generation,Fenton reaction,and combination with other chemical drugs.In this review,we introduce these creative approaches to addressing the hurdles facing PDT in tumors.In particular,the studies that have been validated in animal experiments are preferred in this review over proof-of-concept studies that were only performed in cells.
文摘Current antibody–drug conjugates(ADCs)suffer from low tissue penetration and significant side effects,largely due to the permanent linkage and/or premature release of cytotoxic payloads.Herein,we developed a prodrug–antibody conjugate(ProADC)strategy by conjugating a bioorthogonal-activatable prodrug with an antibody that allowed on-target release and on-demand activation of cytotoxic drugs at a tumor site.The bioorthogonal-caged prodrug exhibited an enhanced permeability into and on-demand activation within cancer cells,while the pH-sensitive ADC linker allowed on-target release of the anticancer agent.Together,the ProADCs showed enhanced tumor penetration and alleviated side effects for use as an on-target and on-demand chemotherapy agents.
基金financially supported by the Key R&D Program of Zhejiang Province (No.2020C03110)the National Natural Science Foundation of China (Nos.T2222021, 32011530115,32025021)+1 种基金the Science&Technology Bureau of Ningbo City (Nos.2020Z094, 2021Z072)Excellent Member of Youth Innovation Promotion Association Foundation of CAS (No.Y2021079)。
文摘Peptide-drug conjugates have achieved considerable development and application as a novel strategy for targeted delivery of anticancer drugs. Bioactive peptides induced calcium deposition can irreversibly assist inhibition of tumors. However, active regulation of calcium level through signal transduction of bioactive substances has not been reported yet. In this study, novel neuropeptide-doxorubicin conjugates(NP-DOX) with lysosome-specific acid response were described for neuropeptide Y_1 receptor(Y_1R)-overexpressed triple-negative breast cancer. The delivery mechanism of NP-DOX was clarified that diverse pathways were involved, including intracellular and intercellular transport. Importantly, up-regulation of Y_1 R-mediated intracellular calcium level via second messenger inositol triphosphate was presented in NP-DOX treated MDA-MB-231 cells. In vivo antitumor efficacy demonstrated that NP-DOX showed less organ toxicity and enhanced tumor inhibition benefited from its controlled release and Y_1R-mediated calcium deposition, compared with free DOX. This bioconjugate is a proof-of-concept confirming that neuropeptide-mediated control of signaling responses in neuropeptide-drug conjugates enables great potential for further applications in tumor chemotherapy.
基金special construction projects fund which belongs to“Taishan Scholar-Pharmacy Specially Recruited Experts”.
文摘Numerous systems have been designed during the past three decades to improve bioavailability of ophthalmic drug delivery,including:ocular prodrugs and nanotechnology-based drug delivery system.The former can improve the efficacy of ocular drug via enhancing corneal penetration of ocular drugs,prolonging their duration of action and/or reducing the systemic side-effects,unfortunately,some characteristics of the pro-drugs,such as poorly aqueous stability,poorly aqueous solubility and severe eye irritation probably,limit their clinical practice and cannot be ignored.As we all know,nanotech-nology for ocular drug delivery can carry poorly soluble drugs,protect the encapsulated molecules from hydrolysis,control the rate of drug delivery and prolong the precorneal retention of drugs.All of these merits may solve the problems in the utilization of ocular prodrugs and increase the bioavailability of ocular drug delivery.By reviewing recent ad-vances of prodrugs and nanostructures in ocular drug delivery,this paper focus specifically on the promising prospects of nanocarriers overcoming the drawbacks of prodrugs for ophthalmic drug delivery by precorneal routes.
文摘Nano materials is a new type of drug carriers with very promising application. In recent years, great progress was achieved in making drugs own the characteristics of targeted and con-trolled release via nanotechnologies. This paper addressed the capability of nano drugs on tar-geting to cells, penetrating through epicyte, controlled release and the security issues re-sulting from its using. We gave the prospect of nano drugs in biology and medicine applying.
